Tuberculous Pleural Effusion in Children

Transcription

1 Iranian Journal of Pediatric Society Volume 2, Number 1, January 2010: Original Article Tuberculous Pleural Effusion in Children Boloursaz MR, Khalilzadeh S, Abbaszadeh M, Velayati AA National Research Institute of Tuberculosis and Lung Disease, Shaheed Beheshti University of Medical Sciences, Tehran, Iran ABSTRACT Background and Aim: Pleural effusion is the second most common type of extra pulmonary tuberculosis with an incidence of 4.9%. This study aims to describe the age distribution, main clinical, laboratory and radiographic findings and outcome of patients with Tuberculous Pleural Effusion (TPE). Materials and Methods: This is a retrospective study of TPE patients admitted in pediatric ward of Masih Daneshvari Hospital from 2002 to Eighteen patients under 18 years of age were included in our study. Results: The patients in our study were 12 boys (66.7%) and 6 girls (33.3%) who were all in the age bracket. The most common presenting symptoms and signs were cough (17 patients, 94.4), anorexia (14 patients, 77.8%), fever (13 patients, 72.2%), chest pain (10patients, 55.6%), tachypnea and respiratory distress (2 patients, 11%), cyanosis (1 patient, 5.5%). All subjects showed exudative pleural fluid with lymphocytosis >50%. Acid fast bacilli (AFB) were not detected in the sputum, gastric and/or pleural fluid of any of the patients. Sputum culture was positive in 4(23.5%). Positive pleural culture was not seen in any of the patients. Pleural biopsies were available in 88% of which showed necrotizing granulomatous inflammation. The most common radiographic findings were unilateral PE (100%), mediastinal lymphadenopathy (22%) and consolidation (11.1%). Eighteen patients received medical treatment. Conclusion: The clinical manifestation of childhood TPE is not specific and especially in countries with high prevalence of TB it should always be considered in the differential diagnosis for older children suffering from parapneumonic effusion. Keywords: Children, Sputum culture, Tuberculous pleural effusion Iranian J Pediatr Soc 2010; 2(1): Corresponding author: Mohammad Reza Boloursaz, M.D. Address: National Research Institute of Tuberculosis and Lung Disease (NRITLD), Shaheed Bahonar Avenue, Darabad, Tehran, Iran Tel: ; Fax: boloursazm@yahoo.com Received: June 2009; Accepted: October 2009 Copyright 2010, Iranian Journal of Pediatric Society. All rights reserved. 15

2 Tuberculous Pleural Effusion INTRODUCTION Tuberculosis (TB) is a significant health problem in developing and under developed countries (1-3). Children account for 5-15% of all tuberculous cases. Although pulmonary tuberculosis is the main manifestation of the disease in childhood, the proportion of extra pulmonary tuberculosis has risen (1). Tuberculous pleural effusion is classified as extra pulmonary disease (4-6). Pleural effusion (PE) is the second most common type of extra pulmonary tuberculosis with an incidence of 4.9% (1,5). Pleural effusion is also more commonly found in patients with TB (7). The frequency of pleural involvement in TB has been variably reported (from 4% in the US to 23% in Spain) (8). Pleural effusion complicated by tuberculosis may be mixed up with other pathogen related pleural effusions (9,10). Effusion is not a common characteristic of primary pulmonary TB in young children and it is more probable to be detected in adolescents and adults (4,11,12). Confirming the diagnosis of tuberculous pleural effusion (TPE) can be difficult because of the classic findings of lymphocytic exudative PE, pleural granuloma, and cutaneous sensitivity to purified protein derivative (PPD) have low specificity and sputum, pleural fluid, and pleural biopsy cultures have a low achievement rate (3,4,7,13). More than 50% of the patients with pleural tuberculosis who are not cured develop pulmonary tuberculosis in the next 5 years (9). Hence, early diagnosis and treatment are clinically significant both for the betterment of patient outcome and in preventing further spread of the disease. Thus, understanding the clinical factors suggestive of tuberculous pleurisy is vital (14). The aim of this study was to describe 1) the age distribution of pediatric patients with tuberculous pleural effusion; 2) main clinical and laboratory findings; and 3) outcome of patient with tuberculous pleural effusion. The decision to conduct such a study was made due to shortage of studies carried out on TPE and considering the fact that Masih Daneshvari hospital is a referral center for pulmonary tuberculosis. MATERIALS AND METHODS This is a retrospective study of patients admitted in the Pediatric ward of Masih Daneshvari hospital with TPE from 2002 to Our study was conducted on 18 patients with less than 18 years of age. The data extracted included epidemiologic, clinical, laboratory (CBC, ESR, CRP, PPD), radiological and pathological findings and pleural fluid analysis. The patients were included in the study if: they showed chest radiograph interpreted by a radiologist as portraying a pleural effusion and at least one of the following criteria 1) positive culture for Mycobacterium tuberculosis from sputum, gastric aspirate, pleural fluid, or pleural biopsy specimen, 2) detection of acid fast bacillus by stain in sputum, gastric aspirate, pleural fluid or pleural tissue (obtained by closed biopsy), 3) the presence of caseating granulomas in histological sections, 4) positive tuberculin test if the palpable induration was 10 mm along with one of the following items: lymphocytic pleural fluid >50%, exudative fluid (protein >4gr/dl or lactate dehydrogenase 200 U/L) or pleural fluid levels of adenosine deaminase greater than 40 Units per liter. Data analysis was carried out with a statistical software package (SPSS, version 16.0; SPSS Inc, Chicago, IL). RESULTS Thirty three patients suffering from pleural effusion were examined from 2002 to 2008; 18 of whom had TPE and were included in our study. Among these patients there were 12 boys and 6 girls who were all between 10 to 18 years of age. Twelve 16 Iranian Journal of Pediatric Society Vol. 2, No. 1, January 2010

3 Boloursaz MR, et al Table 1. Tuberculin test data Tuberculin test, induration (mm) No. % / / / /3 patients (66.67%) had a tuberculin skin test (positive) by induration 10 mm. Tuberculin skin test results are summarized in table 1. Common symptoms among patients were cough (94.4%), anorexia (77.8%) and fever (72.2%). Clinical findings are shown in table 2. History of contact with a TB patient was present in 10 (55.5%); 6 of whom showed PPD 10mm and 4 showed a positive sputum culture. Eleven patients (73.3%) had a positive CRP test assessed semi quantitatively. Fourteen (87.5%) showed high ESR; all of the patients showed exudative pleural fluid. Leukocytosis was not seen in any of the cases. Acid fast bacillus was not observed in sputum, gastric washing or pleural fluid lavage of any of the patients. Sputum culture in 4 of the 18 (23.5%) patients was positive. Table 3 shows the cytological and biochemical analyses of pleural fluid. Radiological records were available in all patients. Chest radiographic findings in all patients with tuberculous pleural effusion are shown in figure 1. Table 2. Clinical findings Finding No. % Malaise 4 22 Fatigue 5 27 Anorexia Respiratory distress 2 11 Dyspnea Tachypnea 2 11 Cough Chest pain Orthopnea Cyanosis Fever Chills Weight loss Decreased breath sounds Figure 1. Radiological features The most common radiographic findings were unilateral pleural effusion (100%), mediastinal lymphadenopathy (22.2%) and parenchymal consolidation (11.1%). Histological finding from pleural biopsy specimens were available in 9 patients; eight (88%) of which showed necrotizing granulomatous inflammation and one had nondiagnostic features, but no one showed positive culture. Hospitalization period was 1 week in 4 patients (22.2%) and 2 weeks in 14 patients (77.8%). Eighteen patients received medical treatment. Average duration of symptoms prior to admission to the hospital in patients with TPE was 30.2 days. Fourteen (77.8%) patients having TPE Table 3. The cytological and biochemical analyses of pleural fluid in the studied patients Laboratory data No. % Cell/L < Lymphocytosis,%>50% Protein <4 (g/dl) > Glucose, g/dl 16 Mean: LDH<500 (U/L) ADA<40 (U/L) > Iranian Journal of Pediatric Society Vol. 2, No. 1, January

4 Tuberculous Pleural Effusion had received antibiotic treatment before final diagnosis. DISCUSSION Our study group included 12 boys (66.7%) and 6 girls (33.3%), ranging in age from years old. In a similar report from Taiwan, boys outnumbered girls; the reported age ranged from 10 to 17 years old (9). Tuberculosis pleural effusion is common in older children, but it is not common in young children (4,9). In contrast TPE was found in young children in a Philippine investigation (3). Tuberculous PE usually appears as an acute illness with fever (72%), cough (94%), and respiratory distress (33.3%). Our findings are similar to those reported from Taiwan and Malaysia (9,15). Results of a report from Pakistan showed fever (97%), cough (91%) and chest pain (80%) as the main clinical manifestations (16). A number of clinical findings (such as fever) reported from a research conducted in Athens was similar to our study (11). The clinical features of childhood TB is not definite. In the present work, patients with TPE frequently had chest pain (56%). A survey from Pakistan revealed chest pain in 80% of their patients (16). Clinical findings, chest radiography, tuberculin skin testing and a history of contact with a case of active pulmonary TB provide a basis for the diagnosis of childhood TB (17-20). A positive tuberculin skin test result is helpful evidence in the diagnosis of TB pleural effusions in areas of low prevalence (or no vaccination). However, a negative tuberculin skin test result may occur in roughly one third of patients (8). In our series, 12 patients (33.3%) showed an induration of 10 mm in the skin test. A history of contact with tuberculous case was present in 10 patients (55.5%). In Taiwan's study positive history was identified in 6 patients (46%) (9). In the present investigation all our patients had normal leukocyte count, while C- reactive protein was normal in seven (27%). In the Taiwanese study, 92% of patients had normal leukocyte count and C-reactive protein was normal in 31% of the patients (9). TPE is usually unilateral (4,8). In our series, unilateral PE was seen in all of the subjects. A research was carried out in Taiwan (2007) and Spain in which unilateral PE was seen in 92% and 100% of patients, respectively (9,4). Mediastinal lymphadenopathy (22.2%) was the most common radiographic feature followed by parenchymal consolidation (11.1%). Parenchymal consolidation was the most common finding reported from a survey conducted in Spain in 2008 (4). Results from Athens study demonstrated mediastinal lymphadenopathy in 33% of the patients (11). Analysis of effusion showed lymphocytic exudative effusion in all our patients. A research from Spain showed lymphocytic fluid in 71% of the patients (4). A neutrophil predominance was not found in our series. In our series, smears and cultures of pleural fluid and pleural biopsy were negative. Tuberculosis is associated with lack of positive cultures of pleural fluid (4). Some reports have shown higher specificity and sensitivity rates for the measurement of ADA activity in the diagnosis of pleural TB (1,4,13). In our series 2 of the 18 patients (11.1%) showed ADA activity <40 U/L (Table 3) which was similar to the results reported by Merino et al (4). Histological examination of pleural biopsy disclosed granulomatous inflammation which is frequently used as a diagnostic test for pleural TB (5,8,12). In our series 8 patients (88%) showed necrotizing granulomatous inflammation. In Merino et al study, 78% of the pleural biopsy specimens showed granulomatous inflammation (4). CONCLUSION Given the prevalence of TPE in developing countries, this disease has to be considered among 18 Iranian Journal of Pediatric Society Vol. 2, No. 1, January 2010

5 Boloursaz MR, et al differential diagnoses for older children and adolescents suffering from parapneumonic effusion. Therefore, prompt diagnosis can prevent adverse effects and progression of the disease. In children with TPE, mediastinal lymphadenopathy and pulmonary parenchymal consolidation are the most frequent radiological findings and correct diagnosis of TPE can be achieved by detecting a normal leukocyte count with an exudative effusion. REFERENCES 1. Mirsha OP, Kumar R, Ali Z, Prasad R, Nath G. Evaluation of polymerase chain reaction (PCR) and adenosine deaminase activity for the diagnosis of tuberculous effusion in children. Arch Dis Child 2006; 91(12): Somu N, Vijayasekaran D, Kavikumar T, Balachandran A, Subramanyam L, Chandrabhushanatn A. Tuberculous disease in a pediatric referral center: 16 years experience. Indian Pediatr 1994; 31: Pama CLP, Gatchalian SR. Clinical profile of cultureproven tuberculosis cases among Filipino children aged 3 months to 18 years. Phil Microbiol Infect Dis 2001; 30(4): Merino JM, Carpintero I, Alvarez T, Rodrigo J, Sanchez J, Coello JM. Tuberculous pleural effusion in children. Chest 1999; 115(1): Seibert AF, Haynes J Jr, Middleton R, Bass Jr JB. Tuberculous pleural effusion. Twenty-year experience. Chest 1991; 99(4): Torgersen J, Dorman SE, Baruch N, Hooper N, Cronin W. Molecular epidemiology of pleural and other extrapulmonary tuberculosis: a Maryland state review. Clin Infect Dis 2006; 42: Merino JM, Alvarez T, Marrero M, Anso S, Elvira A, Eglesias G, et al. Microbiology of pediatric primary pulmonary tuberculosis. Chest 2000; 119(5): Gopi A, Madhavan SM, Sharma SK, Sahn SA. Diagnosis and treatment of tuberculous pleural effusion in Chest 2007; 131(3): Chiu CY, WU JH, Wong KS. Clinical spectrum of tuberculous pleural effusion in children. Pediatr Int 2007; 49(3): Mocelin HT, Fisher GB. Epidemiology, presentation and treatment of pleural effusion. Paediatr Respir Rev 2002; 3(4): Maltezou HC, Spyridis P, Kafetzis DA. Extra-pulmonary tuberculosis in children. Arch Dis Child 2000; 83(4): Cruz AT, Strake JR. Clinical manifestations of tuberculosis in children. Paediatr Respir Rev 2007; 8(2): Villegas MV, Labrada LA, Saravia NG. Evaluation of polymerase chain reaction, adenosine deaminase, and interferon- in pleural fluid for the differential diagnosis of pleural tuberculosis. Chest 2000; 118(5): Lin MT, Wang JY, Yu CJ, Lee LN, Yang PC. Mycobacterium tuberculosis and polymorphonuclear pleural effusion: incidence and clinical pointers. Respir Med 2009; 103(6): Intan HI, Othman N, Alsiddig MF, Wan-Azfa FWZ, Lokman MN. The unexpected bilateral tuberculous empyema: a case report in a child. Int J Health Res 2008; 1(2): Memon SAB, Shaikh SHJ. The etiology of pleural effusion in children: Hyderabad experience. Pak J Med Sci 2007; 23(1): Canete C, Galarza I, Granados A, Farrero E, Estopa R, Manresa F. Tuberculous pleural effusion: experience with six months of treatment with isoniazid and rifampicin. Thorax 1994; 49: World Health Organization. Chapter 1: Introduction and diagnosis of tuberculosis in children-guidelines for national programmes Geneva, Switzerland: WHO, Valdes L, Alvarez D, Valle JM, Pose A, San Jose E. The etiology of pleural effusion in an area with high incidence of tuberculosis. Chest 1996; 109(1): Richter C, Perenboom R, Swai AB, Kitinya J, Mtoni I, Chande H, et al. Diagnosis of tuberculosis in patients with pleural effusion in an area of HIV infection and limited diagnostic facilities. Trop Geogr Med 1994; 46(5): Iranian Journal of Pediatric Society Vol. 2, No. 1, January